AbstractMost human infectious diseases, especially recently emerging pathogens, originate from animals and ongoing disease transmission from animals to people presents a significant global health burden. Recognition of the epidemiologic circumstances involved in zoonotic spillover, amplification and spread of diseases is essential for prioritizing surveillance and predicting future disease emergence risk. We examine the animal hosts and transmission mechanisms involved in spillover of zoonotic viruses to date and discover that viruses with high host plasticity (i.e. taxonomically and ecologically diverse host range) were more likely to amplify viral spillover by secondary human-to-human transmission and have broader geographic spread. Viruses transmitted to humans during practices that facilitate mixing of diverse animal species had significantly higher host plasticity. Our findings suggest that animal-to-human spillover of new viruses that are capable of infecting diverse host species signal emerging disease events with higher pandemic potential in that these viruses are more likely to amplify by human-to-human transmission with spread on a global scale.